109 resultados para acute oral toxicity

em Repositório Institucional UNESP - Universidade Estadual Paulista "Julio de Mesquita Filho"


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Anacardium occidentale L. (Anacardiaceae), popularly known as cajueiro is a native plant to Brazil, and largely used in popular medicine to treat ulcers, hypertension and diarrhea. In the present study, acute, 30-day subacute toxicity and genotoxicity assays were carried out. The crude extract did not produce toxic symptoms in rats in doses up to 2000 mg/kg. Based on biochemical analyses of renal and hepato-biliary functions, such as the level of urea, creatinine, transaminases and alkaline phosphatase, we determined that the extract is generally tolerated by rats. This was also confirmed by hematological and histopathological exams. Genotoxicity was accessed by the Ames test in Salmonella typhimurium strains TA97, TA98, TA 100, TA 102 and by the bone marrow micronucleus test in mice. The extract was shown to induce frameshift, base pair substitution and damage to the chromosomes. However, this effect was less deleterious than the clastogenic effect of ciclophosphamide. (c) 2006 Elsevier B.V.. All rights reserved.

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Dimorphandra mollis is a characteristic plant from Brazilian saP vanna-like vegetation. The pollen of this species could be toxic to bees and the objective of the present investigation was to study the toxicity of methanolic extracts obtained from the flowers, peduncles and stem bark of D. mollis to Apis mellifera workers. For the study, the extracts were incorporated into the diet of the bees for later evaluation of mortality rates. The substances isolated: neoisoastilbin, catechin, astilbin and tannins were tested on adult workers and only catechin did not cause toxic effects. The data obtained in the toxicity bioassays were analyzed statistically by Log Rank test and all methanolic extracts showed significant (p<0.0001) toxic effects. Astilbin is also the major component of pollen grains, and is probably responsible for honeybee mortality during blooming periods.

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The aim of this work was to analyze the acute oral toxicity and the effects on intestinal motility of the extract obtained through decoction 20% (m/v) of Endopleura uchi, popularly known as "uxi-amarelo", a native plant from the Brazilian Amazon. The plant is used indiscriminately against several diseases: arthritis, cholesterol, diabetes, ulcers, myomas, and intestinal illnesses in general, among others. The present results show that there were no significant alterations in intestinal motility and that the extract does not present signs of toxicity, showing its safety for consumption purposes.

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The antinociceptive activity of (-)-spectaline (1), a piperidine alkaloid isolated from Cassia leptophylla Vog. (Leguminosae), was investigated. We have also studied the acute oral toxicity of 1 in mice and it did not show any signals of toxicity in doses lower than 400 mumol/kg. The antinociceptive effect of 1 was evaluated on chemical (acetic acid, formalin and capsaicin) and thermal (hot plate and tail flick) pain models in mice, using classical standard drugs. Dipyrone ID50 = 14.68 mumol/kg (4.8 mg/kg), in-domethacin ID50 = 0.78 mumol/kg (0.28 mg/kg) and (-)-spectaline ID50 = 48.49 mumol/kg (15.75 mg/kg), all produced a significant inhibition of acetic acid-induced abdominal writhing in mice. (-)-Spectaline was inactive in the hyperalgesic model of formalin and did not show any central analgesic activity (hot plate and tail flick models). In the capsaicin-induced neurogenic pain model, (-)-spectaline presented an important inhibitory effect with an ID50 = 20.81 mug/paw and dipyrone ID50 = 19.89 mug/ paw. The ensemble of results permitted us to identify 1 as an antinociceptive compound. The mechanism underlying this antinociceptive effect of 1 remains unknown, but the results suggest that such an effect could be related to pathways associated to vanilloid receptor systems.

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Pós-graduação em Ciências Farmacêuticas - FCFAR

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Two alkaloids, erysodine (1) and erysothrine (2) were isolated from the flowers of a Pakistani medicinal plant, Erythrina suberosa. These compounds were investigated for anxiolytic properties, and the results showed significant effect, in an acute oral treatment with 1-2, which were suspended in saline (NaCl 0.9%) plus DMSO 1%, and evaluated in 122 Swiss male mice exposed to two tests of anxiety - the elevated plus-maze (EPM) and the light/dark transition model (LDTM).

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The effects of acute oral administration of erythrinian alkaloids, Le. (+)-alpha-hydroxy-erysotrine, erythravine and (+)-11 alpha-hydroxy-erythravine isolated from the flowers of Erythrina mulungu were investigated in two animal models of anxiety in mice-the light-dark transition model (LDTM) and the elevated plus-maze (EPM). In the LDTM, erythravine (3, 10 mg/kg) and (+)-11 alpha-hydroxy-erythravine (10mg/kg) increased the time spent by the animals in the illuminated compartment and (+)-11 alpha-hydroxy-erythravine (3 mg/kg) increased the number of transitions between compartments of the LDTM, suggesting an anxiolytic-like effect of these erythrinian alkaloids. Nevertheless, the third alkaloid studied, (+)-alpha-hydroxy-erysotrine, did not change any behavioral response with the range of doses used (3-10 mg/kg). Since the oral administration of the crude extract of E. mulungu (EM) (100-400 mg/kg) did not modify the conventional measures of anxiety in the EPM, this animal model was not chosen to evaluate the anxiolytic properties of the isolated alkaloids. These results suggest that the alkaloids erythravine and (+)-11 alpha-hydroxy-erythravine are responsible for the anxiolytic effects of the crude extract of E. mulungu.